A Perspective on the Permeability of Cocrystals/Organic Salts of Oral Drugs

Molecular Pharmaceutics, Год журнала: 2024, Номер 21(10), С. 4860 - 4911

Опубликована: Сен. 16, 2024

According to the BCS classification system, differentiation of drugs is based on two essential parameters solubility and permeability, meaning latter as pivotal former in creating marketable pharmaceutical products. Nevertheless, indispensable role permeability cocrystal profiles has not been sufficiently cherished, which can be most probably attributed principal reasons. First, responsibility may more user-friendly

Язык: Английский

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Expanding the Crystal Structure Landscape of Pravastatin Complexes: Tuning Solubility, Diffusion, and Pharmacokinetics

Crystal Growth & Design, Год журнала: 2024, Номер 24(12), С. 5309 - 5323

Опубликована: Июнь 1, 2024

Pravastatin (PRV), a lipid-lowering medication, is prescribed to treat cardiovascular disease and dyslipidemia. Due its low permeability high solubility, the biopharmaceutics classification system (BCS) class III drug exhibits poor bioavailability. To overcome bottlenecks of PRV, novel complexes with Zn Cu along zwitterionic cocrystal l-proline (PRO) were synthesized. These new solid forms characterized by SC-XRD, PXRD, DSC, TGA, FT-IR, DVS, SEM images. Rietveld refinement was used obtain 3D coordinates PRV–Na–PRO ionic hydrate from high-resolution PXRD data. PRV–Cu obtained substituting PRV sodium salt Cu/Zn metal. In hydrate, each Na metal coordinated carboxylates (2) PRO (1) three water molecules result in an octahedron geometry. two carboxylate anions molecules, forming square pyramidal The PRV–Zn complex maintains octahedral geometry using four coordination molecules. exhibited higher solubility (1.7-fold) diffusion profile (1.1-fold) compared commercial PRV–Na whereas PRV–Cu/Zn showed controlled release. Surprisingly, enhanced peak plasma concentration Cmax (50 fold) AUC (14.4 during pharmacokinetics study rats. stability supported ground-state optimization energy calculations. Unlike moisture-sensitive PRV–Zn/Cu far superior moisture may offer extended On other hand, significantly improved bioavailability can be commercialized following proper formulation that offers stability.

Язык: Английский

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Density functional theory analyses of an iron-doped nanocage for the adsorption of allopurinol drug towards the development of novel carriers

Computational and Theoretical Chemistry, Год журнала: 2024, Номер 1237, С. 114664 - 114664

Опубликована: Май 25, 2024

Язык: Английский

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Multicomponent Solid Forms of Pioglitazone and Their Influence on Drug Dissolution

Crystal Growth & Design, Год журнала: 2025, Номер 25(5), С. 1514 - 1525

Опубликована: Фев. 13, 2025

Pioglitazone (PIO), a type 2 diabetes medication, effectively decreases blood glucose levels. It exhibits poor aqueous solubility and falls in the category of biopharmaceutics classification system (BCS)-II. To enhance dissolution characteristics lipophilic drug, cocrystallization with organic acids such as 2-naphthalenesulfonoic acid (NSA), oxalic (OXA), maleic (MLE), dihydroxy benzoic (DHBA) were successfully carried out via solvent-drop grinding method. The multicomponent solid forms characterized by powder X-ray diffraction (PXRD), infrared spectroscopy, thermal analysis. crystal structures PIO–NSA PIO–MLE obtained through Rietveld refinement from high-resolution PXRD data their crystallization was challenging. N–H···N hydrogen-bonded PIO homodimer drug is replaced O–H···N neutral hydrogen bond cocrystal monohydrate (PIO–NSA 1:1:1) N+–H···O– ionic interactions salt hemihydrate (PIO–MLE 1:1:0.5). Spectroscopic analysis confirmed formation 1:1 salts between OXA/DHBA. However, structural prediction compromised due to nonmonophasic behavior these salts. Solubility novel performed pH 6.8 phosphate buffer at 37 °C determined using UV–vis spectroscopy. hydrate dissolved 7 times compared PIO, which may be useful for further pharmaceutical application during formulation. correlated synthon modulation, lower melting point, coformer solubility.

Язык: Английский

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Crystal Engineering Strategies for Optimizing Skin Permeation

Crystal Growth & Design, Год журнала: 2025, Номер unknown

Опубликована: Апрель 7, 2025

Язык: Английский

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Synthon Approach in Crystal Engineering to Modulate Physicochemical Properties in Organic Salts of Chlorpropamide

Molecular Pharmaceutics, Год журнала: 2024, Номер 21(6), С. 2894 - 2907

Опубликована: Апрель 30, 2024

The formulation of drug with improved bioavailability is always challenging and indispensable in the field pharmaceutics. control intermolecular interactions via crystal engineering approach solid-state molecular recognition results formation active molecules modulated pharmacological benefits. Therefore, aim to improve solubility dissolution rate chlorpropamide (CPA), mechanochemical liquid-assisted grinding (LAG) several pharmaceutically accepted excipients was performed. This contributed discovery six novel solid phases, namely salts, salt cocrystals cocrystal hydrate─the CPA 3, 4-diaminopyridine (DAP); (SC) polymorph (Z″=3) 1, 4-diazabicyclo [2.2.2] octane (DABCO); a salt, SC (Z″=9), hydrate (Z″=9) piperazine (PIP). these salts are mainly guided by strong hydrogen bonds tunable strength having high electrostatic contribution. attractive interaction brings donor acceptor atoms close each other for facile proton transfer. Furthermore, conformational constraints on molecules, provided directional bonds, quite impressive as this leads identification characterization "new isomers" molecules. new crystalline phases exhibit enhanced intrinsic comparison that pure drug, magnitude being 7, 131, 120 folds CPADAP, CPADABCO_II, CPAPIP_III, respectively. it interesting note order 2.7-, 3-, 7-fold, respectively, abovementioned salts. also mirrors trends binding energy, higher reflected lower solubility. Additionally, vivo experiments performed SD rats enhancement pharmacokinetic properties, when compared pristine drug. concentration CPADABCO_II CPAPIP_III formulations exhibits 6- 4-fold increments, Indeed, corroborate observed structural characterization, energy calculations, solubility, vitro assessments.

Язык: Английский

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Pharmaceutical Salts to Improve Diffusion Permeability of a BCS class III β-blocker Drug Atenolol

CrystEngComm, Год журнала: 2024, Номер 26(45), С. 6420 - 6431

Опубликована: Янв. 1, 2024

Solubility and intestinal permeability of a BCS class III anti-hypertensive drug, atenolol was improved using its glutarate malate salts.

Язык: Английский

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Structural analysis of anti-retroviral drug raltegravir and its potential impurity C: investigation of solubility and stability

CrystEngComm, Год журнала: 2023, Номер 26(4), С. 517 - 531

Опубликована: Дек. 13, 2023

An anhydrous form of raltegravir and two crystalline phases its impurity C were obtained during solid screening their crystal structures are reported with variable conformations.

Язык: Английский

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New Multicomponent Solid Forms of the Antitumor Drug Ripretinib: The Role of Conformations in Dictating Dissolution and Photostability

Crystal Growth & Design, Год журнала: 2024, Номер 24(18), С. 7617 - 7631

Опубликована: Сен. 6, 2024

Язык: Английский

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